Ultrastructural Mucosal Response to Dupilumab in Chronic Rhinosinusitis With Nasal Polyps: A Pilot Study

BACKGROUND: As monoclonal antibodies have proven effective in managing recalcitrant chronic rhinosinusitis with nasal polyps (CRSwNP), the concept of disease remission is evolving, underscoring the need for a comprehensive, multimodal evaluation of disease burden over time. OBJECTIVE: This study first presents ultrastructural changes of the nasal epithelium in patients treated with dupilumab, assessing the potential for mucosal regeneration during long-term follow-up. METHODS: Ten patients (n = 10) were enrolled. Baseline (T0) outcomes included Nasal Polyp Score, Lund-Kennedy Score, 22-item Sinonasal Outcome Test, Visual Analog Scale for nasal symptoms, and CT-scan Lund-Mackay Score. Mucosal samples were collected from the posteromedial aspect of prior antrostomies and analyzed using both light microscopy and transmission electron microscopy (TEM). Outcomes and mucosal sampling were reassessed at 12-month (T1) and compared. Logistic bivariate analysis was performed to assess the relationship between ultrastructural tissue characteristics and clinical outcomes. RESULTS: Significant improvements in all outcomes were observed at T1. A ciliated columnar epithelium was identifiable in most patients (n = 7/10). Intercellular junctions, including desmosomes, tight and adherens junctions, were evident in half of the sample (n = 5/10). Three patients (n = 3/10) showed no evidence of epithelial regrowth. Endoscopic and radiologic outcomes were significantly linked to ultrastructural findings at T1. Higher eosinophilic infiltration at T0 was a positive predictor for the presence of pseudostratified epithelium at T1. CONCLUSIONS: These first preliminary data suggest that ultrastructural response is achievable in most patients with CRSwNP. Larger cohorts are required to strengthen these findings and support the concept of disease remission in course of mAb.